P1599: REAL-WORLD CLINICAL PRACTICES IN TREATMENT DISCONTINUATION WITH COMPLEMENT C5 INHIBITORS FOR ATYPICAL HEMOLYTIC UREMIC SYNDROME: A GLOBAL SURVEY OF HEALTHCARE PROFESSIONALS
Authors: Siu Hing Lo, Daniel Aggio, Francesca Gatta, Moh-Lim Ong, Yan Wang
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by hemolytic anemia, thrombocytopenia and organ damage. Ravulizumab (RAV) and eculizumab (ECU) are complement C5 inhibitors (C5i) approved for the treatment of aHUS. There is limited consensus on treatment duration of C5i and appropriate monitoring after discontinuation for patients with aHUS. Aims: To understand real-world clinical practice of healthcare professionals (HCPs) regarding the discontinuation and re-initiation of C5i for patients with aHUS. Methods: A double-blind cross-sectional online survey (Institutional Review Board-approved) was conducted across Europe, North America and Oceania in 2022. HCPs were eligible if they had ≥6 months experience with C5i for the treatment of patients with aHUS. Survey questions were developed from targeted literature review findings on the personalized treatment of aHUS with RAV and ECU. This survey focused on decisions regarding discontinuation and re-initiation of these C5i treatments. Results: In total, 145 HCPs were surveyed (n=74, 51% with experience prescribing both RAV and ECU), including hematologists (n=83, 57%) and nephrologists (n=52, 36%). The median number of newly diagnosed patients that HCPs treated with C5i within the last two years was 6.0 (interquartile range: 17.0). HCPs provided the estimated proportion of patients with aHUS who were treated with (median [range] 70% [1–100%]) or discontinued (19% [0–100%]) C5i. Those who re-initiated C5i after discontinuation was estimated by hematologists (50% [0–100%]; n=65) and nephrologists (25% [0–100%]; n=37). In addition, 45 HCPs (31%) endorsed the statement ‘I recommend discontinuing treatment and discuss this with the patient’. Most HCPs (n=44/74, 59%) with experience prescribing both RAV and ECU agreed that the important factors to consider when discontinuing C5i differ between RAV and ECU; the Table shows the top five factors from surveyed HCPs when making the decision to discontinue C5i. More than two-thirds of HCPs surveyed ‘often’ or ‘always’ used all markers and tests relating to thrombotic microangiopathy response, hemolysis and kidney function when considering discontinuation of C5i treatment. In addition, 43 HCPs (31%) reported that the minimum treatment duration of C5i should be lifetime. When monitoring patients after C5i discontinuation 102 HCPs (86%) discussed with patients about actions to take when signs, symptoms or triggers occur, monitoring potential triggers (n=89, 75%) and monitoring test results (n=83, 70%). The most common post-discontinuation monitoring tests were serum creatinine, platelet count, hemoglobin and lactate dehydrogenase. To improve C5i discontinuation decision making, HCPs indicated they needed more clinical study data (n=105, 72%), treatment discontinuation guidelines (n=99, 68%), post-discontinuation monitoring guidelines (n=87, 60%), information on relapse risk factors (n=86, 59%) and treatment re-initiation guidelines (n=77, 53%). Summary/Conclusion: Assessment of known aHUS relapse risk factors is essential for decisions on treatment duration and discontinuation. Our findings indicate that there is some commonality among HCPs regarding key factors when considering C5i discontinuation, including kidney function and comorbidities, and their monitoring practice. HCPs need more clinical data and guidance on C5i discontinuation and monitoring, to help with the development of robust personalized treatment strategies for patients with aHUS. Study/medical writing support funder: Alexion, AstraZeneca Rare Disease.Keywords: Monitor, Treatment, Thrombotic microangiopathy, Health care